The aggravating malaria situation in Africa necessitates evaluation of alternative low-cast measures of control. Genetic manipulation of the mosquito vector, reducing its transmission efficiency is such an alternative, with an immense potential for malaria and other vector borne diseases, feasibility of such strategy depends on the processes responsible to spread genes within and between populations of malaria vectors. Thus, I propose to carry out a genetic analysis of populations of A. gambiae, the principal vector of malaria in Africa, that will be used to predict the spread of introduced genes within and between populations over time. Populations separated by potentially important barriers to gene flow will be analyzed on the basis of microsatellite loci and sequence variation in mtDNA and nuclear loci to answer the following questions: 1. what is the size of the basic population unit (deme) in terms of effective population size and geographical area, and how do different environments (habitats) change these dimensions? 2 Do two or more demes occupy the same locale? 3. What effect has distance on gene flow and is it habitat dependent? 4. What is the effect of areas where A. gambiae populations cannot be established e.g., high mountain range, arid land, in restricting gene flow? The description of the genetic structure of populations of A. gambiae obtained by answering those questions will be used to construct a model of the spatial organization of demes, their sizes, and interconnections by gene flow in east Africa. Using computer simulations, changes in the frequency of introduced genes throughout this set of populations (metapopulation) will be predicted. These predictions will allow the resolution of whether or not available means, characterized by (a) efficiency of the genetic drive mechanism; (b) selective value of the introduced genes (c) release effort (i.e., numbers of genetically transformed mosquitoes to be released in a locale and density of release points per area) are adequate to achieve fixation of the introduced genes within an acceptable time period in target populations of A. gambiae.